The research, published in Nature Microbiology, showed that two genetic mutations to the parasite allow it to escape detection.

“This is a serious problem for malaria control efforts and a reminder that pathogens are very capable of adapting to survive,” said senior author Jonathan B. Parr, MD, assistant professor in the division of infectious diseases at the UNC School of Medicine. “Surveillance across the Horn of Africa and alternative malaria diagnostic approaches in affected regions are urgently needed.”

Co-corresponding authors are Sindew M. Feleke, MSc, at the Ethiopian Public Health Institute, Jane Cunningham, MD, at the WHO, and Dr. Parr.

This research project was conducted in partnership with the Ethiopian Public Health Institute and the World Health Organization. The research team enrolled 12,572 participants along Ethiopia’s border with Eritrea, Sudan, and South Sudan, using RDTs, PCR diagnostics, an ultrasensitive immunoassay for antigen detection, and next-generation sequencing to find that P. falciparum lacking the genes histidine-rich protein 2 (pfhrp2) and histidine-rich protein 3 (pfhrp3) escape detection by the RDTs and appear to have spread rapidly.

In collaboration with Brown University’s Jeffrey A. Bailey, MD, PhD, and Ozkan Aydemir, PhD, the researchers applied a molecular sequencing approach to pinpoint the particular deletion patterns of these genetic mutations. “Our method allowed us to study the rich genomic information surrounding these genes in fine detail and at scale, facilitating the identification of evolutionary origins of these deletions,” Aydemir said.

“Our work indicates that prhrp3 deletions have arisen independently multiple times over the course of years,” said Parr, who is a member of the UNC Institute for Global Health and Infectious Diseases. “We also found signs that RDT-based testing and treatment are driving a recent rise in pfhrp2 deletion mutation prevalence, allowing parasites to escape detection.”

In the Nature Microbiology paper, the authors ask, “What other advantages might pfhrp2/3-deleted parasites have over those with intact genes? Our limited understanding of the biology of these deletions makes this question hard to answer.” But the authors posit several lines of inquiry in the paper, though one thing is certain.

Parr said, “We found clear evidence that parasites have recently evolved to escape detection by malaria rapid diagnostic tests along Ethiopia’s borders with Sudan and Eritrea. False-negative results were common in multiple sites and will lead to misdiagnosis and malaria deaths without intervention.”

“The results of this joint research effort have prompted us to change our diagnostic testing policies from HRP2/3-detecting RDTs to non-HRP2/3 targeted RDTs in the most affected regions of Ethiopia,” Feleke said.

Also, along with several other unpublished reports, this study prompted the WHO to issue a statement of concern.

Cunningham, said, “The WHO recommends that all malaria endemic countries start and maintain surveillance for pfhrp2/3 deletions and respond appropriately when they are confirmed, in order to prevent unnecessary morbidity and deaths and to safeguard inroads that have been made towards malaria elimination, particularly in sub-Saharan Africa.”

Understanding living systems, such as tissues formed by cells, poses a significant challenge because of their unique properties, such as adaptation, self-repair and self-propulsion. Nonetheless, they can be studied using models that treat them as just an unusual, “active” form of physical matter. This can reveal extraordinary dynamical or mechanical properties. One of the puzzles is how active materials behave under shear (the deformation produced by moving the top and bottom layers sideways in opposite directions, like sliding microscope cover plates against each other). Researchers at the Institute for Theoretical Physics, University of Göttingen explored this question and discovered a novel type of ordering effect that is generated and sustained by steady shear deformation. The researchers used a computer model of self-propelling particles where each particle is driven by a propulsion force that changes direction slowly and randomly. They found that while the flow of the particles looks similar to that in ordinary liquids, there is a hidden order revealed by looking at the force directions: these tend to point towards the nearest (top or bottom) plate, while particles with sideways forces aggregate in the middle of the system.

“We were exploring the response of a model active material under steady driving, where the system is sandwiched between two walls, one stationary and the other moving to generate shear deformation. What we saw was that at a sufficiently strong driving force, an interesting ordering effect emerges,” comments Dr Rituparno Mandal, Institute for Theoretical Physics at the University of Göttingen. “We now also understand the ordering effect using a simple analytical theory and the predictions from this theory match surprisingly well with the simulation.”

Senior author Professor Peter Sollich, also from the Institute for Theoretical Physics, Universiy of Göttingen, explains, “Often an external force or driving force destroys ordering. But here the driving by shear flow is key in providing mobility to the particles that make up the active material, and they actually need this mobility to achieve the observed order. The results will open up exciting possibilities for researchers investigating the mechanical responses of living matter.”

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“The findings suggest that pediatricians and other primary care providers could use the device to catch amblyopia at an early age when it’s easier to treat,” said Michael F. Chiang, M.D., director of the National Eye Institute (NEI), which supported research and development of the device. NEI is part of the National Institutes of Health.

Amblyopia is impaired vision in one eye and it is the leading cause of preventable monocular (single eye) vision loss, affecting three of every 100 children in the U.S.

During early childhood, our developing brains learn how to take images from each eye and fuse them into a single image to produce vision. Amblyopia develops when misalignment of the eyes (strabismus) or decreased acuity in one eye interferes with the brain’s ability to process visual information from both eyes, causing it to favor one eye. Once a child is visually mature, vision lost in the weaker eye cannot be corrected with glasses or contact lenses.

Children with amblyopia can suffer from poor school performance and impairments in depth perception and fine motor skills such as handwriting and other hand-eye coordinated activities.

Treatment of amblyopia generally involves placing a patch over the good eye to improve vision in the weaker eye. Patching is less successful as children get older, making early detection crucial. However, this depends on timely diagnosis by the child’s doctor, and most pediatricians are equipped only for basic eye chart vision screening tests, which are not useful for detecting amblyopia in very young children.

The screening device works by assessing the eyes’ ability to fixate together. Held 14 inches from the eyes, the child fixates on a smiley face while the device simultaneously scans both retinas. The scan involves a polarized laser that probes nerve fibers in an area of the light-sensing retina called the fovea, which is important for central vision. Even a subtle misalignment of the foveas — called small-angle strabismus — can interfere with the brain’s ability to integrate images from both eyes. The device calculates a binocularity score that indicates whether the child requires referral to an eye health physician for further investigation.

For the study, 300 children, ages 2 to 6 years, with no known eye disorders were recruited during previously scheduled visits to two Kaiser Permanente Southern California pediatric clinics.

Two non-ophthalmic research associates who were trained how to use the device screened each child, and the results were compared against those from an eye examination performed by a pediatric ophthalmologist who was unaware of the device’s results. The device detected all six cases (100% sensitivity) of amblyopia and/or strabismus that had been confirmed by the professional eye examination. The device also flagged an additional 45 children as possibly having amblyopia and/or strabismus who were later determined by the eye examination to be normal (85% specificity).

“In the hands of a trained user, it takes 28 seconds to sit the child down, perform the test, and record the results — provided that the child cooperates — which is an important consideration for its adoption in busy pediatric care settings,” said the study’s co-lead investigator, Shaival S. Shah, M.D., a pediatric ophthalmologist at Kaiser Permanente based in Tustin Ranch, California. The test itself requires just 2.5 seconds of a child’s attention.

A key limitation of the study was that the device was not compared with currently available photo-screening devices. Such devices detect differences in light reflexes in each eye and produce images that can help detect risk factors for amblyopia, but not amblyopia itself, which can result in both over and under detection of amblyopia.

By contrast, the pediatric vision scanner detects the presence of amblyopia as opposed to the risk factors of amblyopia, which may lead to fewer unnecessary referrals to pediatric ophthalmologists.

The pediatric vision screener tested in the study is a prototype of blinq. ®, a device that was cleared by the U.S. Food and Drug Administration in 2016.

The clinical trial identifier is NCT02536963. The study was supported by NEI grant R44EY025926 to Rebiscan, Inc. (doing business as Rebion), the Boston-based firm that markets blinq.®. Support was provided under the Small Business Innovation Research (SBIR) program, a funding mechanism that helps independently owned companies with 500 or fewer employees bring biomedical technologies to the market.

Co-founder of Rebion, David Hunter, M.D., Ph.D., ophthalmologist-in-chief at Boston Children’s Hospital, co-invented blinq.® with support from NEI grant R01EY012883.

Since 2015, scientists of the Leibniz-IZW Cheetah Research Project (CRP) conduct a National Cheetah Survey together with the Namibian Ministry of Environment, Forestry and Tourism (MEFT). The purpose is to obtain data on cheetah density and distribution across the country. Within this framework, a coalition of three cheetah males was captured in the Namib Desert and one animal equipped with a GPS collar. The recorded location and movement data were regularly downloaded during aerial tracking flights. On one of these flights, on October 5^th 2019, the carcass of a collared cheetah — one of the members of the coalition — was located from the aircraft. During the following ground inspection, the other two cheetahs were also found dead. “The GPS data of the collared cheetah revealed that they died within a time window of six hours a few days before we found them,” says Ruben Portas, CRP scientist. “Evaluating their most recent movements, we identified a cluster of GPS locations approximately two kilometres away from the location where they were found dead.” At this spot the cheetahs spent 20 hours on the day before their death. When visiting this cluster, Portas found the carcass of an adult mountain zebra. The GPS and activity data from the collar suggested that the cheetahs fed on it. Bacillus anthracis, the cause of Anthrax infections, was isolated from buccal and nasal swabs collected from the dead zebra, making it the first confirmed anthrax infection in a wildlife species in the Namib Desert.

Carnivores are typically less susceptible to anthrax than herbivores. Cheetahs in particular have a high constitutive innate immunity which provides them with a rapid first line of defence against pathogens such as Bacillus anthracis. “However, when a high load of bacteria is ingested, for example with meat from a contaminated carcass, their potent constitutive innate immunity might be overloaded,” explains CRP project head Bettina Wachter. “Cheetahs scavenge only rarely, which reduces their exposure to anthrax infected prey. As a result, they do not produce high antibody titres, which would be another line of defence. Thus, cheetahs die quickly when infected, as studies in Etosha National Park in northern Namibia have shown.”

The pathogen was not detected in any of the three cheetahs found in the Namib, but the scientists consider it very likely that anthrax was the direct cause of their death. Bacterial cultures from highly susceptible animals that quickly die are often anthrax negative, because the animals might die already at a low presence of bacteria in the blood or from a high load of toxin released by Bacillus anthracis when destroyed by the immune system. Additionally, the vegetative form of the pathogen only develops when exposed to air quickly after the death of the host. The cheetahs were untouched for 11 days after their death and their bodies were not opened by scavengers, which might also explain the negative results of the lab tests for anthrax.

Anthrax is an unstudied disease in arid habitats. When wildlife dies in the Namib Desert, causes are often attributed to drought, hunger and the challenging desert conditions. “The few reported cases in which diseases such as anthrax were tested in the arid environments of Namibia are when livestock or people were directly affected,” says Portas. “We do not know the prevalence of anthrax in the Namib desert and how wildlife populations are affected by the disease. For other habitats, such as the Etosha National Park, there is a large body of research showing that anthrax has a key ecological role in the environment.”

This first confirmed case of anthrax in the Namib Desert in wildlife demonstrates that the disease might by endemic in the desert and other arid environments. Most of the Namib Desert is included in protected areas where cheetahs and other species find an important refuge from conflict with humans. Thus, this new knowledge may be important for assessing risks to the species. “Although few data are available, no other disease has shown such an impact on the cheetah population and certainly requires further research that may lead to appropriate conservation measures,” Wachter concludes. “This study shows that data recorded by GPS collars have the potential to disclose additional important information in addition to spatial movement information.”

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